New Antithrombotics with an Indazole Structure

Fifteen new indazole derivatives have been synthesized. In the Born test, compounds 4f and 4g were most active. They inhibited the blood platelet aggregation induced by collagen with an IC50 = 85 or 90 μM, respectively. After oral administration to rats (60 mg/kg) three of the compounds significantly inhibited the formation of thrombi in arterioles and venules. The strongest effect was observed with 4j which showed an inhibition of 15% in arterioles and 7% in venules. Further experiments showed that compound 4j does not mediate these effects by activating soluble guanylate cyclase, but likely by inhibiting phosphodiesterase isoform PDE 5.